tbuckley/cabot-search huggingface dataset:
Real-world biomarker testing trends in metastatic non-small cell lung cancer (NSCLC).
Authors: Natasha Clinton, Manish R. Patel, Michael Ayars
Journal: Journal of Clinical Oncology (2022)

e18728 Background: NSCLC is now recognized as not one disease, but many—differentiated by an increasing number of molecular targets. About 50% of patients with advanced nonsquamous NSCLC have a targetable driver mutation. We retrospectively assessed biomarker testing trends in a large community oncology practice to identify evolving real-world testing rates and patterns in the areas of methodology, specimen types, and vendors. Methods: Natural-language processing queries were used to extract data from biomarker testing reports of patients diagnosed with stage IV NSCLC in 2015-2019. Tests were included if done within 1 year of diagnosis and were classified as NGS panels (20+ genes) or targeted single-gene tests. Results: Records of 587 patients were included. Over the 5-year study window, testing rates increased for all 6 mutations analyzed (Table). In 2015, only ALK, ROS1, and EGFR were profiled in our data (n = 20 patients), all using targeted single-gene tests. The use of multigene panels increased steadily over time, constituting the majority by 2019. MET, RET, and NTRK were tested almost exclusively using NGS panels (data beginning in 2016). Tissue-only specimens were used for 93.8% of patients diagnosed in 2015, while tissue plus blood were used in 6.3%. Blood-only samples began appearing in our data in 2016, making up 7% of patients. By 2019, the use of blood tests had increased substantially, to 47% of patients, although tissue-only remained the most common type (54%). While blood testing has become more popular, it is often still performed with tissue tests. The primary testing methods used in 2015-2017 were FISH for ALK and ROS1; NGS for MET, NTRK, and RET; and Sanger or NGS for EGFR. By 2018, NGS had become the predominant test method across all 6 biomarkers. During 2015-2016, several vendors were used for testing, with a very segmented market for ALK and EGFR tests. By 2019, the market had aligned to a few key vendors for the majority of tests. In 2016, the top 5 vendors did 76% of 180 total tests, which increased to 93% of 1880 tests in 2019. Almost all blood testing in our data was performed by a single vendor. Conclusions: Testing rates for ALK, ROS1, and EGFR were more consistent than those for MET, RET, and NTRK throughout the study window, possibly because of earlier availability of tests and treatments for these biomarkers. NGS was more available by the time MET, RET, and NTRK became established as actionable biomarkers, explaining the earlier use of panels. A limitation is that nearly 75% of the data are from the final 2 years. These results, however, represent notable testing trends from a large practice and illustrate the expanding application of molecular testing in community oncology.[Table: see text]
Use of breast MRI to distinguish treatment failure versus new primary tumor following single fraction breast intraoperative radiotherapy for breast cancer (SF-IORT).
Authors: Shelby Payne, Sydney Payne, Kathleen C. Horst, Debra M. Ikeda, Frederick M. Dirbas
Journal: Journal of Clinical Oncology (2022)

e12534 Background: Single-fraction, intraoperative radiation therapy (SF-IORT) can replace whole breast radiotherapy (WBT) in select patients after lumpectomy for breast cancer. By combining histology review with co-registration of breast MRI at diagnosis and following an in-breast tumor recurrence, we sought to characterize IBTR as: missed on initial MRI, treatment failure, or new primary tumor. This has important implications for both breast MRI and understanding the effectiveness of SF-IORT. Methods: We reviewed our IORT database for patients with IBTR. Three radiologists recorded findings on DCE-MRI, mammograms and ultrasound, pathology at initial diagnosis and IBTR, and time to IBTR. Results: 90 women received SF-IORT between 12/6/2002 - 4/10/2019. There were 6 IBTRs (average age at recurrence 63, range 49-71 years). For these 6 patients, initial diagnostic mammograms showed fatty (1), scattered (4) or extremely dense (1) breasts with suspicious masses (4), calcifications (1), or asymmetry (1), average size 1.4 cm: range 0.3 - 2.0 cm. On MRI, background parenchymal enhancement was minimal (2), mild (2), moderate (1), or marked (1), showing a mass (4), mass/distortion (1), or post-biopsy marker/no abnormal enhancement (1). Initial pathology showed 2 IDC, 3 IDC/DCIS, and 1 DCIS, (average size 1.7 cm, range 1.1 - 2.4 cm) with 6/6 ER +, 5/6 PR + and 6 HER2 negative. IDC Ki-67 ranged from 5-25%. 5/6 patients had sentinel lymph node biopsy (SLNB) with 1/5 having a positive SLN. 4/6 received endocrine therapy. One patient declined follow-up mammography. After IORT, IBTR (average size 1.4 cm, range 0.7 - 3.6 cm) was diagnosed by mammography (3), palpable breast lump (2), or palpable axillary lymph node (LN) (1) shown as mass (4), mass/calcifications (1), or abnormal LN (1). IBTR occurred post-SF-IORT an average of 141.7 months, range 88.3 to 195.8 months. 2/6 IBTR occurred near the biopsy cavity. Subsequent surgery included mastectomy (3), re-excision lumpectomy/RT (2), or axillary LN dissection/RT (1) showing 4 IDC, 1 IDC/DCIS, and 1 IDC /ILC (6/6 ER +; 3/6 PR positive; 2 PR weakly positive; and 5 HER2 negative, 1 HER2 equivocal). Ki-67 ranged from 1-70%. Conclusions: 6/90 (6.6%) patients had an IBTR an average of 141.7 months post SF-IORT with 2/6 near the biopsy cavity. Breast MRI reliably screens patients for SF-IORT. Co-registration of imaging can help distinguish true recurrences from new primary tumors.
Clinical outcomes in immunotherapy and chemotherapy in minority populations with non-small cell lung cancer (NSCLC).
Authors: Sang Ha Shin, Teresita Gonzalez, Luis E. Raez, Shenae Samuels, Syed Razi, Atif Mahmoud Hussein
Journal: Journal of Clinical Oncology (2022)

e20508 Background: Lung cancer is the leading cause of cancer deaths for Hispanics (HIS). Similarly, non-Hispanic blacks (NHB) are often disproportionately represented among cancer deaths compared to other racial/ethnic groups with lung cancer being the second most common cancer in black men and women, as well as the leading cause of cancer death. Despite these statistics, HIS and NHB remain underrepresented in non-small cell lung cancer (NSCLC) research. The aim of this study was to determine if there was a difference in outcomes between HIS, NHB and NH Whites (NHW) who had NSCLC and were treated with surgery, immunotherapy or chemotherapy. Methods: We studied 645,221 observations from the 2004-2018 National Cancer Database (NCDB), categorized as HIS, NHB or NHW, who received surgery, immunotherapy or chemotherapy for NSCLC. Categorical variables were analyzed using Pearson’s chi-square test or Fisher’s exact test. Continuous variables were analyzed using ANOVA. Survival outcomes were assessed using a Cox regression model and Kaplan-Meier curves with log-rank tests. Results: Regardless of treatment types, HIS had the highest median overall survival (OS) compared to other groups (NHW: 14.7 months; NHB: 15.0 months; HIS: 16.4 months) (P &lt; 0.001). Regardless of the type of systematic therapy received (immunotherapy or chemotherapy), HIS had the highest median OS (P &lt; 0.001) with HIS in the immunotherapy cohort having the highest survival advantage of all other race/ethnicity and chemotherapy groups. Multivariate Cox regression model further support the survival advantage of HIS compared to NHW (HR = 0.86; P = 0.009). OS was also assessed between patients who received surgery and/or chemotherapy. Patients who received a combination of surgery and chemotherapy had the highest OS compared to patients who underwent surgery only or received chemotherapy only. Among the cohort who received both, HIS had the highest median OS (NHW: 55.2 months; NHB: 55.5 months; HIS: 61.5 months). The surgery only cohort had the next highest median OS of all treatment groups; however, the HIS ethnicity group was non-estimable due to the small sample size. Of all three treatment groups, the chemotherapy only cohort had the lowest median OS while HIS had the highest median OS (NHW: 11.8 months; NHB: 12.9 months; H: 13.5 months) (P &lt; 0.001). Conclusions: Results of our study suggest immunotherapy may offer an increased survival advantage for HIS and NHB compared to chemotherapy. For patients receiving chemotherapy, a combination of surgery and chemotherapy may offer a greater survival advantage for NSCLC patients. Hispanic ethnicity was associated with better survival regardless of the type of treatment received.
Insulin-like growth factor 1 and its binding protein-2 in tumor and peritumoral tissues as important factors involved in recurrence of soft tissue sarcomas in older men.
Authors: Susan A. Sagatelyan, Irina V. Kaplieva, Elena M. Frantsiyants, Irina A. Goroshinskaya, Larisa N. Vashchenko, Pavel V. Chernogorov, Tatiana V. Ausheva, Yulia A. Pogorelova, Polina S. Kachesova, Marina A. Gusareva, Dmitriy P. Atmachidi, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e23556 Background: The system of insulin-like growth factors (IGF) is involved in the pathogenesis of many malignant tumors. At the same time, the specificity of this system in recurrent soft tissue sarcomas is unknown. The purpose of this study was to analyze the IGF system in tumors and their peritumoral areas in men with recurrent soft tissue sarcomas. Methods: The study included 26 men aged 57.8±6.2 years with primary (n = 12, group 1, controls) and recurrent (n = 14, group 2, main group) soft tissue sarcoma of the extremities, T2bN0M0. Grade 1 tumors were diagnosed in 6 patients of group 1 and in 7 patients of group 2, while the other patients had G3 or G4 tumors. 95% of tumors were liposarcomas. All patients of group 2 had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Levels of the IGF system components were determined in tumor (T) and peritumoral (PT) tissues by ELISA, and ratios of IGF(T)/IGF(PT) were calculated. Results: Levels of the IGF system components in patients of group 1 were similar in T and PT. In group 2, levels of IGF1 and IGFВР2 in T were respectively 2.2 and 1.6 times (p &lt; 0.05) lower than in PT, but did not differ significantly from the levels in group 1. The IGF1(T)/IGF1(PT) ratio in patients of group 2 was 1.8 times (p &lt; 0.05) lower than in group 1. PT levels of IGF2 in group 2 depended on the tumor grade: they were 1.5 times (p &lt; 0.05) higher in G1 than in G3-G4, while no such dependence was observed in T. Conclusions: The levels of the IGF system components in recurrent soft tissue sarcomas in older men had some peculiarities. Unlike primary sarcomas with similar levels of the studied components of the IGF system in tumors and in peritumoral tissues, recurrent tumors contained less IGF1 and IGFBP2 than the corresponding peritumoral areas. The levels of IGF2 in the peritumoral tissues of recurrent tumors depended on the tumor grade.
Higher proportions of CD39+ tumor-resident cytotoxic T cells predict recurrence-free survival in patients with stage III melanoma treated with adjuvant immunotherapy
Authors: Grace Heloise Attrill, Carina N Owen, Tasnia Ahmed, Ismael A Vergara, Andrew J Colebatch, Jordan W Conway, Kazi J Nahar, John F Thompson, Ines Pires da Silva, Matteo S Carlino, Alexander M Menzies, Serigne Lo, Umaimainthan Palendira, Richard A Scolyer, Georgina V Long, James S Wilmott
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Adjuvant immune checkpoint inhibitor (ICI) immunotherapies have significantly reduced the recurrence rate in high-risk patients with stage III melanoma compared with surgery alone. However, 48% of anti-PD-1-treated patients will develop recurrent disease within 4 years. There is a need to identify biomarkers of recurrence after adjuvant ICI to enable identification of patients in need of alternative treatment strategies. As cytotoxic T cells are critical for the antitumor response to anti-PD-1, we sought to determine whether specific subsets were predictive of recurrence in anti-PD-1-treated high-risk patients with stage III melanoma. Methods Associations with recurrence in patients with stage III melanoma were sought by analyzing resection specimens (n=103) taken prior to adjuvant nivolumab/pembrolizumab±low-dose/low-interval ipilimumab. Multiplex immunohistochemistry was used to quantify intratumoral CD8+ T-cell populations using phenotypical markers CD39, CD103, and PD-1. Results With a median follow-up of 19.3 months, 37/103 (36%) of patients had a recurrence. Two CD8+ T-cell subpopulations were significantly associated with recurrence. First, CD39+ tumor-resident memory cells (CD39+CD103+PD-1+CD8+ (CD39+ Trm)) comprised a significantly higher proportion of CD8+ T cells in recurrence-free patients (p=0.0004). Conversely, bystander T cells (CD39−CD103−PD-1−CD8+) comprised a significantly greater proportion of T cells in patients who developed recurrence (p=0.0002). Spatial analysis identified that CD39+ Trms localized significantly closer to melanoma cells than bystander T cells. Multivariable analysis confirmed significantly improved recurrence-free survival (RFS) in patients with a high proportion of intratumoral CD39+ Trms (1-year RFS high 78.1% vs low 49.9%, HR 0.32, 95% CI 0.15 to 0.69), no complete lymph node dissection performed, and less advanced disease stage (HR 2.85, 95% CI 1.13 to 7.19, and HR 1.29, 95% CI 0.59 to 2.82). The final Cox regression model identified patients who developed recurrence with an area under the curve of 75.9% in the discovery cohort and 69.5% in a separate validation cohort (n=33) to predict recurrence status at 1 year. Conclusions Adjuvant immunotherapy-treated patients with a high proportion of CD39+ Trms in their baseline melanoma resection have a significantly reduced risk of melanoma recurrence. This population of T cells may not only represent a biomarker of RFS following anti-PD-1 therapy, but may also be an avenue for therapeutic manipulation and enhancing outcomes for immunotherapy-treated patients with cancer.
ATRT-04. Clinical and (epi)genetic characterisation of patients with atypical teratoid/rhabdoid tumor (ATRT) and extracranial malignant rhabdoid tumor conceived following assisted reproduction technologies (ART)
Authors: Karolina Nemes, Martin Benesch, Julia Kolerova, Pascal Johann, Martin Hasselblatt, Christian Thomas, Susanne Bens, Olga Liaugaudiene, Alireza Sadeghipour, Nicolas von der Weid, Irene Schmid, Corrie Gidding, Anat Erdreich-Epstein, Claudia Khurana, Georg Ebetsberger-Dachs, Andreas Lemmer, Carmen Hernández Marqués, Ziad Khatib, Jane Pears, Franz Quehenberger, Jaclyn A Biegel, Reiner Siebert, Michael C Frühwald
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Anecdotal case reports suggest an association between assisted reproduction technologies (ART) and malignant rhabdoid tumors (MRT). We performed a multi-institutional retrospective analysis of the EU-RHAB database, complemented by additional cases outside of EU-RHAB to compile clinical, (epi)genetic characteristics and outcome data of children with MRT following ART. METHODS: Data of 14 patients (from 311 patients with MRT) from 9 countries were analyzed (2010-2018). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and sequencing. Molecular subgroups were determined using DNA methylation arrays and correlated with a validation cohort (n=22, tumor samples of MRT; n=39 blood samples of patients small for gestational age). RESULTS: The median age at diagnosis of the 13 girls and 1 boy was 9 months (0 – 66). 8 patients with ATRT, 3 with extracranial, extrarenal-, 1 with renal rhabdoid tumor and 2 with synchronous tumors were identified. Distant metastases at diagnosis were present in 6 patients. A germline mutation (GLM) was detected in 5 patients. In 11 tumors complete data on SMARCB1 mutational status were available. DNA methylation subgrouping was available in 10 tumors and 6 blood samples. A female predominance was noted as compared to the EU-RHAB cohort with MRT born without ART (n=213, p=0.009). A total of 8 patients received gross total resection, n=12 patients received conventional chemotherapy (EU-RHAB=9, Head Start II=2, IRS III=1). Radiotherapy was applied to 6 patients. 10 patients achieved CR, and 5 remain in continuing CR. Significant genome-wide DNA methylation differences (including imprinted genes) between patients born after ART and patients born without ART could not be demonstrated. CONCLUSIONS: Long-term survival is achievable in patients who develop MRT after ART, even in cases with GLM, metastatic disease at diagnosis, or relapse. Larger epidemiological studies are needed to confirm a potential association between MRT and ART.
Dietary quality in early-onset gastrointestinal malignancies: NHANES 2005-2018.
Authors: Mir Lim, Suleyman Yasin Goksu, Jude Khatib, Sarah Reddy, Shaalan Shaalan Beg, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2022)

3549 Background: The incidence of early-onset colorectal, stomach, esophageal, and pancreatic cancer, which occur in individuals &lt;50 years of age, is rising worldwide. However, little is known about why rates have been up trending. Previous studies have linked poor diet and nutrition to an increased risk of typical-onset gastrointestinal (GI) malignancies. In this study, we aimed to describe dietary quality in individuals with early-onset GI malignancies and compare it to typical-onset GI malignancies. Methods: We queried the 2005-2018 National Health and Nutrition Examination Survey (NHANES) database for all survey participants diagnosed with GI malignancies, including colorectal, esophageal, gallbladder, liver, pancreas, rectal, and stomach cancer. We classified early and typical-onset GI cancer based on age of diagnosis of &lt;50 and ≥50 years, respectively. Participants &lt;50 without a history of cancer were classified as controls. We assessed the dietary quality by calculating the healthy eating index score (HEI-2015) from NHANES database for all participants. The primary outcome was mean HEI-2015 score for early onset GI malignancies. We performed propensity score weighted analysis to balance gender, race, income, education level, and BMI between the groups. We used logistic regression analysis to assess the relationship between early-onset GI malignancies and HEI-2015 quintiles. Results: Out of 32,235 participants in NHANES database, 330 individuals (1%) reported a diagnosis of GI malignancy. Sixty-eight (20.5%) individuals had early-onset GI malignancies. We identified 17,420 controls who were &lt;50 years old with no reported history of malignancy. Fifty-three percent of early-onset GI cancers were female vs 47% of typical-onset GI cancers; 59% vs 59% were non-Hispanic White; 66% vs 40% had a college degree; 13% vs 7% had high income and 40% vs 36% were obese. The mean HEI-2015 score in early-onset GI cancer was 52.9 (SD 14.7) compared to 53.6 (SD 13.0) in typical-onset GI cancers, which was not significantly different (p=0.72). There was no significant association between poor HEI-2015 scores in individuals with early-onset vs typical-onset GI malignancies on logistic regression analysis (OR 0.84 [0.35-2.03]). In addition, HEI-2015 quintiles were not significantly associated with those with early-onset GI malignancies compared to controls &lt;50 years old (OR 2.06 [0.72-5.9]). Conclusions: The diet quality of early-onset GI malignancies does not align with the national Dietary Guidelines. However, in this analysis of the NHANES database, we did not find a significant difference in HEI-2015 scores between early-onset versus typical-onset GI malignancies.
Bronchodilators in bronchiectasis: there is light but it is still too dim
Authors: Mario Cazzola, Miguel Ángel Martínez-García, Maria Gabriella Matera
Journal: European Respiratory Journal (2022)

<b>Despite the fact that the first large randomised controlled trial on the effect of bronchodilators in bronchiectasis has now been published, more information in this field is urgently needed</b>https://bit.ly/3Fhy6Hf
Sacral Neuromodulation with the InterStim™ system for lower urinary tract dysfunctions (SOUNDS): 5-Year results of clinical effectiveness, Quality of Life, patient-reported outcomes and safety in a French multicenter observational study
Authors: E. Chartier-Kastler, A. Ruffion, L. Le Normand, D.U.J. Keller, J.-N. Cornu
Journal: European Urology (2022)
Bereavement practices of gynecologic oncologists: Physician and care team practices compared to caregiver needs.
Authors: Lauren Harrison, Christopher M. Morosky, Bradford Whitcomb
Journal: Journal of Clinical Oncology (2022)

12021 Background: Gynecologic cancers account for over 34,000 deaths in the United States annually. Family-centered care is beneficial to the family unit and patient throughout the illness course. Research is lacking regarding how physicians should approach family members or other caregivers after a patient dies. We aimed to assess how gynecologic oncologists are currently practicing and compare that to family members’ needs during the bereavement period. Methods: We devised a set of paired surveys that were distributed to the Society for Gynecologic Oncology and to patient families. Families were recruited using social media, publicizing in local organizations, and advertising in University of Connecticut campus-wide emails. Likert-scale style questions with responses ranging from “1” to “10” were used to assess opinions on aspects of bereavement care and reported as means. Differences in means were assessed using ANOVA and T-tests and considered to be statistically significant if the P-value was &lt; 0.05. Results: We received completed surveys from 129 physicians and 17 caregivers from different families. 48% of physicians reported contacting patient families, and, similarly, 47% of family members reported receiving contact from physicians. Physicians had a mean 6.21/10 confidence level (where 10 is maximum confidence) in providing bereavement care, while families reported 5.76/10 confidence in their physician’s ability to provide bereavement support ( P = 0.493). Factors that influenced physicians confidence in providing bereavement support were undergoing formal training in bereavement (6.84/10 vs 5.14/10 for physicians who had not been trained, P &lt; 0.001) and being in practice for more than 11 years (5.65/10 for ≤10 years in practice, 7.05 for ≥11 years, P = 0.001). Physicians who contacted patients personally had a higher confidence level (6.98/10) in providing bereavement support compared with those who did not contact families (5.51/10, P &lt; 0.001). Family members were nearly unanimous in reporting a desire for physicians to contact them personally (16/17), and stated that a phone call (56%) or a sympathy card (38%) were their preferred methods of contact. Conclusions: Our study suggests that although families appreciate contact from physicians after their loss, physicians do not have a high level of confidence in providing this support. Physicians who undergo bereavement training and who reached out after patients had died have higher confidence levels in interacting with family members. Based on these results, formal bereavement training should be incorporated into gynecologic oncology fellowships in order to increase the comfort levels and likelihood of gynecologic oncologists reaching out to families after a patient has died.